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TRK RECEPTORS: ROLES IN NEURONAL SIGNAL TRANSDUCTION
Trk receptors are a family of three receptor tyrosine kinases, each of which can be activated by one or more of four neurotrophins-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophins 3 and 4 (NT3 and NT4). Neurotrophin signaling through these receptors regulates ce...
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Published in: | Annual review of biochemistry 2003-01, Vol.72 (1), p.609-642 |
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Main Authors: | , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Trk receptors are a family of three receptor tyrosine kinases, each of which
can be activated by one or more of four neurotrophins-nerve growth factor
(NGF), brain-derived neurotrophic factor (BDNF), and neurotrophins 3 and 4 (NT3
and NT4). Neurotrophin signaling through these receptors regulates cell
survival, proliferation, the fate of neural precursors, axon and dendrite
growth and patterning, and the expression and activity of functionally
important proteins, such as ion channels and neurotransmitter receptors. In the
adult nervous system, the Trk receptors regulate synaptic strength and
plasticity. The cytoplasmic domains of Trk receptors contain several sites of
tyrosine phosphorylation that recruit intermediates in intracellular signaling
cascades. As a result, Trk receptor signaling activates several small G
proteins, including Ras, Rap-1, and the Cdc-42-Rac-Rho family, as well as
pathways regulated by MAP kinase, PI 3-kinase and phospholipase-C-γ
(PLC-γ). Trk receptor activation has different consequences in different
cells, and the specificity of downstream Trk receptor-mediated signaling is
controlled through expression of intermediates in these signaling pathways and
membrane trafficking that regulates localization of different signaling
constituents. Perhaps the most fascinating aspect of Trk receptor-mediated
signaling is its interplay with signaling promoted by the pan-neurotrophin
receptor p75
NTR
. p75
NTR
activates a distinct set of
signaling pathways within cells that are in some instances synergistic and in
other instances antagonistic to those activated by Trk receptors. Several of
these are proapoptotic but are suppressed by Trk receptor-initiated signaling.
p75
NTR
also influences the conformations of Trk receptors; this
modifies ligand-binding specificity and affinity with important developmental
consequences. |
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ISSN: | 0066-4154 1545-4509 |
DOI: | 10.1146/annurev.biochem.72.121801.161629 |